Influence of Trypanosoma cruzi strain on the pathogenesis of chronic myocardiopathy in mice

Abstract

The murine model of chronic Chaga's myocardiopathy was developed in 201 inbred and outbred mice. The experimental groups consisted of 1st: 73 inbred AKR and A/J mice inoculated with one of the following Trypanosoma cruzi strains: Peruvian (Type I), 12 SF (Type II) or Colombian (Type III); 2nd: 128 outbred Swiss mice, chronically infected either with Type II or Type III strains isolated from human patients from different geographical areas. All T. cruzi strains were previously characterized by their morphobiological behaviour in mice and by isoenzymatic patterns. For the 1st group the inoculum was 5 x 10(4) for the Peruvian strain and 1 x 10(5) for the 12 SF and Colombian strains. In the 2nd group-Swiss mice the inoculum size varied from 2 x 10(4) to 2 x 10(5). The inbred animals were killed at a 3 time-point scale (90, 180 and 240 days) post-infection. The Swiss mice were killed from 180 to 660 days after infection. The evaluation of parasitemia and serology (xenodiagnosis and indirect immunofluorescent test) was performed. The incidence of macroscopic alterations of the heart and cardiac index were evaluated. Histopathological lesions of the myocardium were graded. The influence of T. cruzi strain on the intensity of cardiac lesions was evaluated by the Chi-square test; the incidence of inflammatory lesions and its relationship to the parasite strain was evaluated by the Fisher test. The influence of the duration of infection was evaluated by using the Gamma Coefficient of Kruskal and Goodman and its measure of significance. Slight to severe microscopic alterations occurred in 85% of the chronically infected mice. There were a clear predominance on the incidence and intensity of inflammatory and fibrotic alterations for the mice infected with Type III strains. Statistical analysis has shown significant differences among the infected groups, in the inflammatory and fibrotic lesions. Macroscopic alterations (right cavities dilatation and apex aneurism of left ventricle), differed in incidence according to mice strains; in Swiss and AKR mice, significant differences were seen in mice infected with different T. cruzi strains, but the A/J mice failed to show significant differences correlated with different parasite strains. The duration of infection, from 90 to 240 days, could not be correlated with the degree of lesions in the several groups.

Selection of Trypanosoma cruzi clonal genotypes (clonet 20 and 39) isolated from Bolivian triatomines following subculture in liquid medium

“…cruzi consists of a pool of clonal populations circulating among humans, domestic and sylvatic vectors and mammalian reservoirs, which have evolved in a great diversity with distinct biological, immunological and biochemical characteristics (Dvorak 1984, Sanchez et al 1990, Andrade 1990). Identification of strains or clones is indispensable in order to study the variable characteristics of the populations.…”

Early electrocardiographic abnormalities in Trypanosoma cruzi-seropositive children.

“…20 Experimentally, it has been described that some T. cruzi strains induce more cardiac damage than others. 21 However, attempts to establish a relationship between parasite genetic markers and clinical manifestation have failed. 22,23 The data obtained in this study are unique and cause concern considering that such an epidemiologic and clinical situation still exists at the same time as a major success is claimed by the ''Southern Cone Initiative'' for the elimination of vectorial transmission of Chagas' disease.…”

The pathogenesis of Chagas' disease: when autoimmune and parasite-specific immune responses meet

“…Decades of investigations using this experimental model have taught us that both host and parasite genetic backgrounds contribute to disease development. Thus, certain mouse strains will develop CChC after infection with some strains of T. cruzi, but not with others (Andrade 1990, Andrade et al 1985. A model that closely resembles the human disease has been studied in our laboratories.…”